title: The transcription factors Blimp-1 and IRF4 jointly control the differentiation and function of effector regulatory T cells.
abstract: Regulatory T cells (T(reg) cells) are required for peripheral tolerance. Evidence indicates that T(reg) cells can adopt specialized differentiation programs in the periphery that are controlled by transcription factors usually associated with helper T cell differentiation. Here we demonstrate that expression of the transcription factor Blimp-1 defined a population of T(reg) cells that localized mainly to mucosal sites and produced IL-10. Blimp-1 was required for IL-10 production by these cells and for their tissue homeostasis. We provide evidence that the transcription factor IRF4, but not the transcription factor T-bet, was essential for Blimp-1 expression and for the differentiation of all effector T(reg) cells. Thus, our study defines a differentiation pathway that leads to the acquisition of T(reg) cell effector functions and requires both IRF4 and Blimp-1.
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
authors.forename: Erika
authors.initials: E
authors.lastname: Cretney
authors.forename: Annie
authors.initials: A
authors.lastname: Xin
authors.forename: Wei
authors.initials: W
authors.lastname: Shi
authors.forename: Martina
authors.initials: M
authors.lastname: Minnich
authors.forename: Frederick
authors.initials: F
authors.lastname: Masson
authors.forename: Maria
authors.initials: M
authors.lastname: Miasari
authors.forename: Gabrielle T
authors.initials: GT
authors.lastname: Belz
authors.forename: Gordon K
authors.initials: GK
authors.lastname: Smyth
authors.forename: Meinrad
authors.initials: M
authors.lastname: Busslinger
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Nutt
authors.forename: Axel
authors.initials: A
authors.lastname: Kallies
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics*; D002478:Cells, Cultured; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D050835:Interferon Regulatory Factors / Q000235:genetics* / Q000378:metabolism; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D000074462:Positive Regulatory Domain I-Binding Factor 1; D011485:Protein Binding; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012689:Sequence Homology, Nucleic Acid; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D000099218:Interferon Regulatory Factor-4
chemical_list: D049452:Green Fluorescent Proteins; D050835:Interferon Regulatory Factors; D016753:Interleukin-10; D000074462:Positive Regulatory Domain I-Binding Factor 1; D014157:Transcription Factors; D000099218:Interferon Regulatory Factor-4; C513258:Prdm1 protein, mouse